Diisopropylethylamine → di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

HRID 2105020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2105020
[Br:1][C:2]1[N:3]=[C:4]([CH:26](Cl)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.CCN(C(C)C)C(C)C.[NH2:48][C:49]1[CH:50]=[C:51]2[C:56](=[CH:57][CH:58]=1)[C:55]([N:59]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[N:54][CH:53]=[CH:52]2>CC#N.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[N:3]=[C:4]([CH:26]([NH:48][C:49]2[CH:50]=[C:51]3[C:56](=[CH:57][CH:58]=2)[C:55]([N:59]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:67]([O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:68])=[N:54][CH:53]=[CH:52]3)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 688168844-bromo-2-(chloro(5-ethyl-2-fluoro-3-methoxyphenyl)methyl)-1-trityl-1H-imidazole

Produkt 1

HCID 86607941di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonateAusbeute 78,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution of the chloro intermediate (350 mg, 0.594 mmol) in 5 mL CH3CN and 2 mL CH2Cl2 at rt, was added DIEA (0.207 mL, 1.19 mmol), di-tert-butyl (6-aminoisoquinolin-1-yl)imidodicarbonate (235 mg, 0.653 mmol). The mixture was stirred at rt for 18 h and at 40° C. for 3 h, then was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 425 mg of Intermediate 206.4 as a colorless residue.

Aufarbeitung

  1. washThe organic phase was washed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-ccd74af2b5864045b4ebd8df98b32efb
Quelldatensatz
uspto-grants-2009_08
Patentnummer
US07576098B2

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